crossing96/oncoscreening huggingface dataset:
Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence.	Epirubicin, gemcitabine, and pirarubicin are widely used as first-line drugs for intravesical chemotherapy to prevent tumor recurrence after transurethral bladder tumor resection for non-muscle-invasive bladder cancer (NMIBC). However, which drug is better is less discussed. A total of 335 NMIBC patients administered intravesical chemotherapy underwent transurethral bladder tumor resection (TURBT) in our hospital from October 2015 to October 2019. After TURBT, all the patients received standard intravesical chemotherapy. Through clinical data collection and telephone follow-up, the tumor recurrence and adverse reactions of all patients after bladder perfusion treatment were counted. Recurrence was defined as new tumor appearance in the bladder. Of the 335 patients who underwent intravesical chemotherapy, 109 patients received epirubicin and 114 patients and 112 patients were given gemcitabine and pirarubicin, respectively. According to the general information of the patients, the patients were divided into intermediate-risk and high-risk bladder cancer and compared separately. There was no statistical difference in clinical and pathological features between different groups (P > 0.05). The recurrence rate of intermediate-risk bladder cancer patients shows no difference between three groups (P > 0.05). As for the high-risk bladder cancer patients, it is found that the 1-year recurrence rate between three groups was not statistically significant (P > 0.05), whereas the 2-year recurrence rate of patients given gemcitabine (9.87%) was significantly lower than that of epirubicin (25.37%) and pirarubicin (24.32%), and the difference was statistically significant (P < 0.017, Bonferroni adjusted P value). The Kaplan-Meier survival curves showed that the recurrence-free survival rate of patients received gemcitabine was significantly higher than that of the other two groups. Comparing the incidence of adverse reactions during the infusion of the three groups of patients, the differences were not statistically significant (P > 0.05). In patients with high-risk non-muscle-invasive bladder cancer, the application of gemcitabine intravesical chemotherapy is related with a relatively lower recurrence rate but similar incidence of adverse reactions.	bladder
Bladder Cancer in a Long-term Survivor of the Prune Belly Syndrome.	Prune belly syndrome (PBS) is a rare but morbid complexity of congenital anomalies that consists of abdominal wall defect, bilateral cryptorchidism, and urinary tract dilation. With the recent advances in perinatal care, the life expectancy of patients with PBS has improved. Although renal and sexual outcomes are frequently discussed in the literature, little is known about urinary tract malignancies in adulthood. Herein, we present a case of advanced bladder cancer in a 38-year-old man with PBS. To the best of our knowledge, a malignant tumor arising in a nondefunctionalized or nonaugmented bladder in patients with PBS has not been reported previously.	bladder
[Immunotherapy in advanced urothelial cancer].	Cisplatin containing chemotherapy has proven benefit for muscle-invasive locally advanced and metastatic urothelial cancer. The carboplatin based combinations are less effective in these settings. In most cases for the platinum based chemotherapy ineligible patients only the best supportive care could be given. The treatment options have expanded in the past few years with the introduction of systemic immunotherapy with checkpoint inhibitors. We review the relevant clinical trials' data which can completely transform the treatment landscape of locally advanced or metastatic urothelial cancer.	bladder
[Pathology of tumors of the urinary bladder, aspects and expectations of the histological report (TUR, cystectomy)].	"Urothelial tumors are among the most frequently occurring malignancies. The patients' clinical outcome can be diverse after recognition of the presence of the tumor. The result of the histology report (grade, histologic subtype, stage) makes remarkable impact on treatment strategies. There are innumerable papers (debates) in the literature concerning the best methods in classification, stage determination, application of immunohistochemical markers (to possibly avoid false negative, false positive results) and the use of molecular biological examinations. The authors attempt to draw attention on the everyday diagnostic difficulties of the ""general pathologist"", through their own experience and the latest reports of the literature."	bladder
Indeterminate atypia in urinary tract cytology: Does it really matter?	The study of atypia in urinary cytology has been ongoing for decades but most studies have focused primarily on test performance in patients with concurrent biopsies and/or limited follow-up periods. While these data are useful, many studies fail to consider patient factors that may alter the pretest probability, which can subsequently affect test performance. An isolated diagnosis of malignancy in urinary cytology usually has a high positive predictive value and allows a urologist to conduct a rigorous workup of the patient to establish a tissue diagnosis. However, it is less certain how an atypical diagnosis impacts patient care, given that many patients have a history of bladder cancer and are already under surveillance with cystoscopy at regular screening intervals. Furthermore, a discrete negative urine cytology is unlikely to allow a patient to forego a cystoscopy procedure due to limitations in the sensitivity of urine cytology. Over the last several years, the introduction of The Paris System for Reporting Urinary Cytology (TPS) has improved the predictive value of atypical diagnoses, but additional studies are needed to evaluate the performance of these diagnoses in specific clinical situations. Such data could better inform urologists on how to manage patients with atypical diagnoses. This review discussed the diagnosis of atypia in urinary cytology and the impact of such a diagnosis in various clinical contexts.	bladder
Epigenetic Priming of Bladder Cancer Cells With Decitabine Increases Cytotoxicity of Human EGFR and CD44v6 CAR Engineered T-Cells.	BACKGROUND: Treatment of B-cell malignancies with CD19-directed chimeric antigen receptor (CAR) T-cells marked a new era in immunotherapy, which yet has to be successfully adopted to solid cancers. Epigenetic inhibitors of DNA methyltransferases (DNMTi) and histone deacetylases (HDACi) can induce broad changes in gene expression of malignant cells, thus making these inhibitors interesting combination partners for immunotherapeutic approaches. METHODS: Urothelial carcinoma cell lines (UCC) and benign uroepithelial HBLAK cells pretreated with the DNMTi decitabine or the HDACi romidepsin were co-incubated with CAR T-cells directed against EGFR or CD44v6, and subsequent cytotoxicity assays were performed. Effects on T-cell cytotoxicity and surface antigen expression on UCC were determined by flow cytometry. We also performed next-generation mRNA sequencing of inhibitor-treated UCC and siRNA-mediated knockdown of potential regulators of CAR T-cell killing. RESULTS: Exposure to decitabine but not romidepsin enhanced CAR T-cell cytotoxicity towards all UCC lines, but not towards the benign HBLAK cells. Increased killing could neither be attributed to enhanced target antigen expression (EGFR and CD44v6) nor fully explained by changes in the T-cell ligands PD-L1, PD-L2, ICAM-1, or CD95. Instead, gene expression analysis suggested that regulators of cell survival and apoptosis were differentially induced by the treatment. Decitabine altered the balance between survival and apoptosis factors towards an apoptosis-sensitive state associated with increased CAR T-cell killing, while romidepsin, at least partially, tilted this balance in the opposite direction. Knockdown experiments with siRNA in UCC confirmed BID and BCL2L1/BCLX as two key factors for the altered susceptibility of the UCC. CONCLUSION: Our data suggest that the combination of decitabine with CAR T-cell therapy is an attractive novel therapeutic approach to enhance tumor-specific killing of bladder cancer. Since BID and BCL2L1 are essential determinants for the susceptibility of a wide variety of malignant cells, their targeting might be additionally suitable for combination with immunotherapies, e.g., CAR T-cells or checkpoint inhibitors in other malignancies.	bladder
Magnetic resonance imaging-based radiomics signature for preoperative prediction of Ki67 expression in bladder cancer.	PURPOSE: The Ki67 expression is associated with the advanced clinicopathological features and poor prognosis in bladder cancer (BCa). We aimed to develop and validate magnetic resonance imaging (MRI)-based radiomics signatures to preoperatively predict the Ki67 expression status in BCa. METHODS AND MATERIALS: We retrospectively collected 179 BCa patients with Ki67 expression and preoperative MRI. Radiomics features were extracted from T2-weighted (T2WI) and dynamic contrast-enhancement (DCE) images. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (low Ki67 expression group) in the training set. Minimum redundancy maximum relevance was used to identify the best features associated with Ki67 expression. Support vector machine and Least Absolute Shrinkage and Selection Operator algorithms (LASSO) were used to construct radiomics signatures in training and SMOTE-training sets, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. The decision curve analyses (DCA) and calibration curve and were used to investigate the clinical usefulness and calibration of radiomics signatures, respectively. The Kaplan-Meier test was performed to investigate the prognostic value of radiomics-predicted Ki67 expression status. RESULTS: 1218 radiomics features were extracted from T2WI and DCE images, respectively. The SMOTE-LASSO model based on nine features achieved the best predictive performance in the SMOTE-training (AUC, 0.859; accuracy, 80.3%) and validation sets (AUC, 0.819; accuracy, 81.5%) with a good calibration performance and clinical usefulness. Immunohistochemistry-based high Ki67 expression and radiomics-predicted high Ki67 expression based on the SMOTE-LASSO model were significantly associated with poor disease-free survival in training and validation sets (all P < 0.05). CONCLUSIONS: The SMOTE-LASSO model could predict the Ki67 expression status and was associated with survival outcomes of the BCa patients, thereby may aid in clinical decision-making.	bladder
Preliminary Functional Outcome Following Robotic Intracorporeal Orthotopic Ileal Neobladder Suspension with Round Ligaments in Women with Bladder Cancer.	BACKGROUND: Chronic urinary retention (CUR) is a frequent complication after orthotopic neobladder (ONB) reconstruction in women. To decrease CUR, several open surgical modifications to provide back support to the ONB have been established on the basis of pelvic anatomical differences between females and males. OBJECTIVE: To illustrate our technique for robotic intracorporeal reconfiguration of ONB as integrated into our open surgical approach to provide back support to the ONB with round ligaments in women. DESIGN, SETTING, AND PARTICIPANTS: From November 2017 to April 2021, 28 patients underwent robotic intracorporeal ONB with a minimum of 6 mo of follow-up at a single centre. SURGICAL PROCEDURE: We performed robotic radical cystectomy, pelvic lymphadenectomy, and a complete intracorporeal ONB suspended with round ligaments (rONB). Our surgical procedure is demonstrated in the accompanying video. MEASUREMENTS: Demographics and clinical and pathological data were collected. Perioperative and 90-d complications and 6-mo functional outcomes were compared for the rONB group (n = 12) and the patients receiving a traditional ONB (tONB; n = 16). RESULTS AND LIMITATIONS: The median total operative time was 305 min (interquartile range [IQR] 270-370) for tONB and 303 min (IQR 287-330) for rONB. The median estimated blood loss was 325 ml (IQR 200-700) for tONB and 350 ml (IQR 262-600) for rONB. Some 50% of the tONB group and 41.7% of the rONB group experienced low-grade complications. A total of 12.5% tONB and 8.3% rONB patients experienced high-grade complications with neobladder-vaginal fistula. The cumulative risk of CUR was 37.5% in the tONB group and 16.7% in the rONB group. This study is limited by the small sample size and the short follow-up period. CONCLUSIONS: We established a feasible surgical technique for a robotic intracorporeal ONB configuration suspended with round ligaments. This may prevent the occurrence of emptying dysfunction in women. PATIENT SUMMARY: We describe our stepwise technique for creating a new bladder within the body that is suspended with round ligaments. Patients undergoing removal of the bladder for bladder cancer may benefit from this technique in terms of better urinary function and the advantages of a robotic surgical approach.	bladder
Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer.	BACKGROUND: Bladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients' survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection. METHOD: A total of 12 patients with BC and 4 non-cancerous participants (as healthy control) were recruited from a single center between March 2018 and December 2019 as the discovery set. Midstream urine samples from each participants were collected and high-throughput sequencing and differentially expression analysis were conducted. Combined with miRNA expression profile of BC tissue from The Cancer Genome Atlas (TCGA), miRNAs biomarkers for BC were determined. Candidate miRNAs as biomarkers were selected followed by verification with a quantitative reverse-transcription polymerase chain reaction assay in an independent validation cohort consisting of 53 BC patients and 51 healthy controls. The receiver-operating characteristic (ROC) curve was established to evaluate the diagnostic performance of UE-derived miRNAs. The possible mechanism of miRNAs were revealed by bioinformatic analysis and explored in vitro experiments. RESULTS: We identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in UEs from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort. Subsequently, the performance to discover BC of the miR-93-5p, miR-516a-5p was further verified with an area under ROC curve (AUC) of 0.838 and 0.790, respectively, which was significantly higher than that of urine cytology (AUC = 0.630). Moreover, miR-93-5p was significantly increased in muscle-invasive BC compared with non-muscle-invasive BC with an AUC of 0.769. Bioinformatic analysis revealed that B-cell translocation gene 2(BTG2) gene may be the hub target gene of miR-93-5p. In vitro experiments verified that miR-93-5p suppressed BTG2 expression and promoted BC cells proliferation, invasion and migration. CONCLUSION: Urine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC. In vitro experiments suggested that miR-93-5p overexpression may contribute to BC progression via suppressing BTG2 expression.	bladder
A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer.	Activation of natural killer (NK) cell function is regulated by cytokines, such as IL-2, and secreted factors upregulated in the tumor microenvironment, such as platelet-derived growth factor D (PDGF-DD). In order to elucidate a clinical role for these important regulators of NK cell function in antitumor immunity, we generated transcriptional signatures representing resting, IL-2-expanded, and PDGF-DD-activated, NK cell phenotypes and established their abundance in The Cancer Genome Atlas bladder cancer (BLCA) dataset using CIBERSORT. The IL-2-expanded NK cell phenotype was the most abundant in low and high grades of BLCA tumors and was associated with improved prognosis. In contrast, PDGFD expression was associated with numerous cancer hallmark pathways in BLCA tumors compared with normal bladder tissue, and a high tumor abundance of PDGFD transcripts and the PDGF-DD-activated NK cell phenotype were associated with a poor BLCA prognosis. Finally, high tumor expression of transcripts encoding the activating NK cell receptors, KLRK1 and the CD160-TNFRSF14 receptor-ligand pair, was strongly correlated with the IL-2-expanded NK cell phenotype and improved BLCA prognosis. The transcriptional parameters we describe may be optimized to improve BLCA patient prognosis and risk stratification in the clinic and potentially provide gene targets of therapeutic significance for enhancing NK cell antitumor immunity in BLCA.	bladder
Clinical trajectory of a patient with filaminopathy who developed arrhythmogenic cardiomyopathy, myofibrillar myopathy, and multiorgan tumors.	We report a case of a patient presenting with arrhythmogenic cardiomyopathy, myofibrillar myopathy, and multiorgan tumors. A 41-year-old woman with a history of hypertrophic cardiomyopathy, diagnosed at 6 years of age, developed scoliosis after puberty. Following spinal surgery to address the scoliosis, she developed recurrent severe arrhythmia and heart failure. She developed hypoventilation at age 29 years. Proximal dominant weakness and mild elevation of serum creatine kinase indicated possible myopathy. Myofibrillar myopathy was diagnosed by muscle biopsy at age 30 year. Acute abdomen was repeatedly reported from age 33 years, eventually leading to a diagnosis of gastric polyp and erosive ulcer. A urinary bladder tumor was found at age 35 years, and breast cancer was diagnosed at age 40 years. Whole exome sequencing detected a heterozygous missense mutation in Filamin C. Recent evidences suggest that filamins are associated with tumors, and this case further highlights the clinical spectrum of filaminopathy.	bladder
Should patients with non-muscle-invasive bladder cancer discontinue fibrin clot inhibitors during bacille Calmette-Guérin?	OBJECTIVE: To determine the impact of fibrin clot inhibitor (FCI) use on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate bacille Calmette-Guérin (BCG). PATIENTS AND METHODS: We performed an Institutional Review Board-approved review of patients with NMIBC treated with adequate intravesical BCG, at our institution between 2000 and 2018. FCI use at the time of BCG therapy was recorded for each patient. Patients were stratified according to use of FCI medication. Recurrence- and progression-free survival were analysed using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: Overall, 226 of 526 patients (43.0%) used a FCI: aspirin (205), clopidogrel (38), warfarin (18) and novel oral anticoagulant (NOAC; seven). The use of FCIs did not adversely affect either recurrence- or progression-free survival (P = 0.385 and P = 0.131, respectively). These results did not change when the impact of aspirin, clopidogrel or warfarin/NOAC use on recurrence and progression was evaluated separately. On multivariate analysis, FCI use was neither associated with tumour recurrence nor progression. CONCLUSION: The use of FCIs was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for NMIBC. Based on these results, FCIs may be safely continued during BCG immunotherapy.	bladder
A retrospective study on optimal number of cycles of the first-line platinum-based chemotherapy for metastatic urothelial carcinoma.	BACKGROUND: Recently, switch maintenance with avelumab has been approved for the treatment of advanced or metastatic urothelial carcinoma (UC), with no progression after four to six cycles of first-line platinum-based chemotherapy. However, the optimal number of cycles of platinum-based chemotherapy has not been determined. OBJECTIVE: To analyze the clinical characteristics of patients with advanced UC who were treated with platinum-based chemotherapy and investigate the association between the number of cycles of the treatment and the patients' overall survival. METHODS: A total of 124 patients with advanced UC who were treated with first-line platinum-based chemotherapy at Osaka City University Hospital between April 2009 and January 2020 were retrospectively reviewed. RESULTS: Of the 124 patients, clinical information regarding overall survival was available for 115 patients. The median age was 72 years (range, 43-95 years). Only 59 patients (51.3 %) were treated with gemcitabine and cisplatin, and 52 patients (45.2 %) were treated with gemcitabine and carboplatin. The median number of cycles was three (1-8), and the percentage of patients who discontinued chemotherapy due to progressive disease was 80.3%, 64.0%, and 86.4% in those receiving one to three, four, and five or more cycles, respectively. Moreover, no difference in overall survival was observed between patients who received four cycles and those who received five or more cycles at both univariate and multivariate levels. CONCLUSIONS: The present study shows that five or more cycles of first-line platinum-based chemotherapy did not prolong overall survival compared with four cycles, suggesting that four cycles of chemotherapy might be sufficient, considering the new treatment strategy involving switch maintenance with avelumab.	bladder
Gene regulatory networks analysis of muscle-invasive bladder cancer subtypes using differential graphical model.	BACKGROUND: Recently, erdafitinib (Balversa), the first targeted therapy drug for genetic alteration, was approved to metastatic urothelial carcinoma. Cancer genomics research has been greatly encouraged. Currently, a large number of gene regulatory networks between different states have been constructed, which can reveal the difference states of genes. However, they have not been applied to the subtypes of Muscle-invasive bladder cancer (MIBC). RESULTS: In this paper, we propose a method that construct gene regulatory networks under different molecular subtypes of MIBC, and analyse the regulatory differences between different molecular subtypes. Through differential expression analysis and the differential network analysis of the top 100 differential genes in the network, we find that SERPINI1, NOTUM, FGFR1 and other genes have significant differences in expression and regulatory relationship between MIBC subtypes. CONCLUSIONS: Furthermore, pathway enrichment analysis and differential network analysis demonstrate that Neuroactive ligand-receptor interaction and Cytokine-cytokine receptor interaction are significantly enriched pathways, and the genes contained in them are significant diversity in the subtypes of bladder cancer.	bladder